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Doxorubicin-poly (ethylene glycol)-alendronate self-assembled micelles for targeted therapy of bone metastatic cancer.

Ye WL, Zhao YP, Li HQ, Na R, Li F, Mei QB, Zhao MG, Zhou SY - Sci Rep (2015)

Bottom Line: In pH 5.0 phosphate buffer solution (PBS), the micelle released DOX significantly faster than in pH 7.4 PBS.Finally, DOX loaded DOX-hyd-PEG-ALN micelle effectively delayed the tumor growth, decreased the bone loss and reduced the cardiac toxicity in tumor-bearing nude mice as compared with free DOX.In conclusion, DOX loaded DOX-hyd-PEG-ALN micelle had potential in treating bone metastatic tumor.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.

ABSTRACT
In order to increase the therapeutic effect of doxorubicin (DOX) on bone metastases, a multifunctional micelle was developed by combining pH-sensitive characteristics with bone active targeting capacity. The DOX loaded micelle was self-assembled by using doxorubicin-poly (ethylene glycol)-alendronate (DOX-hyd-PEG-ALN) as an amphiphilic material. The size and drug loading of DOX loaded DOX-hyd-PEG-ALN micelle was 114 nm and 24.3%. In pH 5.0 phosphate buffer solution (PBS), the micelle released DOX significantly faster than in pH 7.4 PBS. In addition, with the increase of incubation time, more red DOX fluorescence was observed in tumor cells and trafficked from cytoplasm to nucleus. The IC50 of DOX loaded DOX-hyd-PEG-ALN micelle on A549 cells was obviously lower than that of free DOX in 48 h. Furthermore, the in vivo image experimental results indicated that a larger amount of DOX was accumulated in the bone metastatic tumor tissue after DOX loaded DOX-hyd-PEG-ALN micelle was intravenously administered, which was confirmed by histological analysis. Finally, DOX loaded DOX-hyd-PEG-ALN micelle effectively delayed the tumor growth, decreased the bone loss and reduced the cardiac toxicity in tumor-bearing nude mice as compared with free DOX. In conclusion, DOX loaded DOX-hyd-PEG-ALN micelle had potential in treating bone metastatic tumor.

No MeSH data available.


Related in: MedlinePlus

Cytotoxicity free DOX and DOX loaded DOX-hyd-PEG-ALN micelle on A549 cells in 24 h (A) and 48 h (B). Data are presented as the average ± standard deviation (n = 5). *p < 0.05 vs DOX at the same concentration of free DOX.
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f9: Cytotoxicity free DOX and DOX loaded DOX-hyd-PEG-ALN micelle on A549 cells in 24 h (A) and 48 h (B). Data are presented as the average ± standard deviation (n = 5). *p < 0.05 vs DOX at the same concentration of free DOX.

Mentions: The cytotoxicity of DOX loaded DOX-hyd-PEG-ALN micelle on A549 cells is showed in Fig. 9A,B. The IC50 of free DOX and DOX-loaded DOX-hyd-PEG-ALN micelle is showed in Table 2. The results indicated that there was no significantly difference in cytotoxicity between free DOX and DOX loaded DOX-hyd-PEG-ALN micelle when they were cultured with A549 cells for 24 h. However, after A549 cells were cultured with DOX loaded DOX-hyd-PEG-ALN micelle for 48 h, DOX loaded DOX-hyd-PEG-ALN micelle showed significantly higher anticancer activity at the dose of 40 μg/mL as compared with the same dose of free DOX. These results indicated that the DOX loaded DOX-hyd-PEG-ALN micelle was efficiently uptaken by A549 cells to produce the desired antitumor effect. The low anticancer activity of DOX loaded DOX-hyd-PEG-ALN micelle in 24 h was probably caused by the time-consuming DOX release from micelle and DOX trafficking from endolysosome to the nucleus in A549 cells.


Doxorubicin-poly (ethylene glycol)-alendronate self-assembled micelles for targeted therapy of bone metastatic cancer.

Ye WL, Zhao YP, Li HQ, Na R, Li F, Mei QB, Zhao MG, Zhou SY - Sci Rep (2015)

Cytotoxicity free DOX and DOX loaded DOX-hyd-PEG-ALN micelle on A549 cells in 24 h (A) and 48 h (B). Data are presented as the average ± standard deviation (n = 5). *p < 0.05 vs DOX at the same concentration of free DOX.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588583&req=5

f9: Cytotoxicity free DOX and DOX loaded DOX-hyd-PEG-ALN micelle on A549 cells in 24 h (A) and 48 h (B). Data are presented as the average ± standard deviation (n = 5). *p < 0.05 vs DOX at the same concentration of free DOX.
Mentions: The cytotoxicity of DOX loaded DOX-hyd-PEG-ALN micelle on A549 cells is showed in Fig. 9A,B. The IC50 of free DOX and DOX-loaded DOX-hyd-PEG-ALN micelle is showed in Table 2. The results indicated that there was no significantly difference in cytotoxicity between free DOX and DOX loaded DOX-hyd-PEG-ALN micelle when they were cultured with A549 cells for 24 h. However, after A549 cells were cultured with DOX loaded DOX-hyd-PEG-ALN micelle for 48 h, DOX loaded DOX-hyd-PEG-ALN micelle showed significantly higher anticancer activity at the dose of 40 μg/mL as compared with the same dose of free DOX. These results indicated that the DOX loaded DOX-hyd-PEG-ALN micelle was efficiently uptaken by A549 cells to produce the desired antitumor effect. The low anticancer activity of DOX loaded DOX-hyd-PEG-ALN micelle in 24 h was probably caused by the time-consuming DOX release from micelle and DOX trafficking from endolysosome to the nucleus in A549 cells.

Bottom Line: In pH 5.0 phosphate buffer solution (PBS), the micelle released DOX significantly faster than in pH 7.4 PBS.Finally, DOX loaded DOX-hyd-PEG-ALN micelle effectively delayed the tumor growth, decreased the bone loss and reduced the cardiac toxicity in tumor-bearing nude mice as compared with free DOX.In conclusion, DOX loaded DOX-hyd-PEG-ALN micelle had potential in treating bone metastatic tumor.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.

ABSTRACT
In order to increase the therapeutic effect of doxorubicin (DOX) on bone metastases, a multifunctional micelle was developed by combining pH-sensitive characteristics with bone active targeting capacity. The DOX loaded micelle was self-assembled by using doxorubicin-poly (ethylene glycol)-alendronate (DOX-hyd-PEG-ALN) as an amphiphilic material. The size and drug loading of DOX loaded DOX-hyd-PEG-ALN micelle was 114 nm and 24.3%. In pH 5.0 phosphate buffer solution (PBS), the micelle released DOX significantly faster than in pH 7.4 PBS. In addition, with the increase of incubation time, more red DOX fluorescence was observed in tumor cells and trafficked from cytoplasm to nucleus. The IC50 of DOX loaded DOX-hyd-PEG-ALN micelle on A549 cells was obviously lower than that of free DOX in 48 h. Furthermore, the in vivo image experimental results indicated that a larger amount of DOX was accumulated in the bone metastatic tumor tissue after DOX loaded DOX-hyd-PEG-ALN micelle was intravenously administered, which was confirmed by histological analysis. Finally, DOX loaded DOX-hyd-PEG-ALN micelle effectively delayed the tumor growth, decreased the bone loss and reduced the cardiac toxicity in tumor-bearing nude mice as compared with free DOX. In conclusion, DOX loaded DOX-hyd-PEG-ALN micelle had potential in treating bone metastatic tumor.

No MeSH data available.


Related in: MedlinePlus